1-24652579-C-T

Variant names:

• chr1-24652579-C-T
• rs1009577703
• NM_005839.4:c.871C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005839.4(SRRM1):​c.871C>T​(p.Arg291Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,408 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R291P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SRRM1 NM_005839.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14
• Publications: 0 publications found

Genes affected

SRRM1 (HGNC:16638): (serine and arginine repetitive matrix 1) Enables RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Located in nuclear speck. Part of catalytic step 2 spliceosome. Biomarker of gestational diabetes. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005839.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRM1	NM_005839.4	MANE Select	c.871C>T	p.Arg291Cys	missense	Exon 7 of 17	NP_005830.2
	SRRM1	NM_001366595.1		c.871C>T	p.Arg291Cys	missense	Exon 7 of 18	NP_001353524.1	A0A0S2Z4Z6
	SRRM1	NM_001366569.1		c.871C>T	p.Arg291Cys	missense	Exon 7 of 18	NP_001353498.1	A0A994J7V4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRM1	ENST00000323848.14	TSL:1 MANE Select	c.871C>T	p.Arg291Cys	missense	Exon 7 of 17	ENSP00000326261.8	Q8IYB3-1
	SRRM1	ENST00000596378.1	TSL:1	c.754C>T	p.Arg252Cys	missense	Exon 7 of 15	ENSP00000471084.1	M0R088
	SRRM1	ENST00000928582.1		c.871C>T	p.Arg291Cys	missense	Exon 7 of 19	ENSP00000598641.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152014 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461394 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 727002

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.0000224 AC: 1 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86126

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111838

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152014 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41364

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.1
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.32		Gain of catalytic residue at R291 (P = 0.087)
MVP		0.32
MPC		0.50
ClinPred		0.98	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.66
gMVP		0.35
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1009577703; hg19: chr1-24979070;